AMMONIA N 13- ammonia n-13 injection, solution
The University of Texas Southwestern Medical Center
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use AMMONIA N 13 INJECTION safely and effectively. See full prescribing information for AMMONIA N 13 INJECTION.
AMMONIA N 13 INJECTION for intravenous use
Initial U.S. Approval: 2007
INDICATIONS AND USAGE
Ammonia N 13 Injection is a radioactive diagnostic agent for Positron Emission Tomography (PET) indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease (1).
DOSAGE AND ADMINISTRATION
Rest Imaging Study(2.1):
Stress Imaging Study(2.2):
DOSAGE FORMS AND STRENGTHS
Glass vial containing 0.138 – 1.387 GBq (3.75 mCi/mL – 37.5 mCi/mL) of Ammonia N 13 Injection in aqueous 0.9 % sodium chloride solution (approximately 8 mL volume)(3).
WARNINGS AND PRECAUTIONS
Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker(5).
No adverse reactions have been reported for Ammonia N 13 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting system(6).
To report SUSPECTED ADVERSE REACTIONS, contact UT Southwestern Medical Center at 214-645-7611 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
Ammonia N 13 Injection is indicated for diagnostic Positron Emission Tomography (PET) imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease.
To increase renal clearance of radioactivity and to minimize radiation dose to the bladder, ensure that the patient is well hydrated before the procedure and encourage voiding as soon as a study is completed and as often as possible thereafter for at least one hour.
The converted radiation absorbed doses in rem/mCi are shown in Table 1. These estimates are calculated from the Task Group of Committee 2 of the International Commission on Radiation Protection.1
Glass vial (30 mL) containing 0.138-1.387 GBq (3.75 mCi/mL – 37.5 mCi/mL) of Ammonia N 13 Injection in aqueous 0.9 % sodium chloride solution (approximately 8 mL volume) that is suitable for intravenous administration.
Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration(2.4)].
No adverse reactions have been reported for Ammonia N 13 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems. However, the completeness of these sources is not known.
The possibility of interactions of Ammonia N 13 Injection with other drugs taken by patients undergoing PET imaging has not been studied.
Pregnancy Category C
Animal reproduction studies have not been conducted with Ammonia N 13 Injection. It is also not known whether Ammonia N 13 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ammonia N 13 Injection should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Ammonia N 13 Injection, use alternative infant nutrition sources (e.g. stored breast milk or infant formula) for 2 hours (>10 half-lives of radioactive decay for N 13 isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of Ammonia N 13 Injection has been established in pediatric patients based on known metabolism of ammonia, radiation dosimetry in the pediatric population, and clinical studies in adults [see Dosage and Administration(2.4)].
Ammonia N 13 Injection is a positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient, [13N] ammonia, has the molecular formula of 13NH3with a molecular weight of 16.02, and has the following chemical structure:
Ammonia N 13 Injection is provided as a ready to use sterile, pyrogen-free, clear and colorless solution. Each mL of the solution contains between 0.138 GBq to 1.387 GBq (3.75 mCi to 37.5 mCi) of [13N] ammonia, at the end of synthesis (EOS) reference time, in 0.9% aqueous sodium chloride. The pH of the solution is between 4.5 to 7.5. The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of 0.05-0.1 picomoles (8.47-16.94 picograms) of ammonia.
Nitrogen N13 decays by emitting positron to Carbon C13 (stable) and has a physical half-life of 9.96 minutes. The principal photons useful for imaging are the dual 511 keV gamma photons that are produced and emitted simultaneously in opposite direction when the positron interacts with an electron (Table 2).
|Positron(β+)||100||1190 keV (Max.)|
The specific gamma ray constant (point source air kerma coefficient) for nitrogen N13 is 5.9 R/hr/mCi (1.39 x 10-6 Gy/hr/kBq) at 1 cm. The half-value layer (HVL) of lead (Pb) for 511 keV photons is 4 mm. Selected coefficients of attenuation are listed in Table 3 as a function of lead shield thickness. For example, the use of 39 mm thickness of lead will attenuate the external radiation by a factor of about 1000.
|Shield Thickness (Pb) mm||Coefficient of Attenuation|
Table 4 lists fractions remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide.
Ammonia N 13 Injection is a radiolabeled analog of ammonia that is distributed to all organs of the body after intravenous administration. It is extracted from the blood in the coronary capillaries into the myocardial cells where it is metabolized to glutamine N 13 and retained in the cells. The presence of ammonia N 13 and glutamine N 13 in the myocardium allows for PET imaging of the myocardium.
Following intravenous injection, ammonia N 13 enters the myocardium through the coronary arteries. The PET technique measures myocardial blood flow based on the assumption of a three-compartmental disposition of intravenous ammonia N 13 in the myocardium. In this model, the value of the rate constant, which represents the delivery of blood to myocardium, and the fraction of ammonia N 13 extracted into the myocardial cells, is a measure of myocardial blood flow. Optimal PET imaging of the myocardium is generally achieved between 10 to 20 minutes after administration.
Following intravenous injection, Ammonia N 13 Injection is cleared from the blood with a biologic half-life of about 2.84 minutes (effective half-life of about 2.21 minutes). In the myocardium, its biologic half-life has been estimated to be less than 2 minutes (effective half-life less than 1.67 minutes).
The mass dose of Ammonia N 13 Injection is very small as compared to the normal range of ammonia in the blood (0.72-3.30 mg) in a healthy adult man [see Description(11.1)].
Plasma protein binding of ammonia N 13 or its N 13 metaboliteshas not been studied.
Ammonia N 13 undergoes a five-enzyme step metabolism in the liver to yield urea N 13 (the main circulating metabolite). It is also metabolized to glutamine N 13 (the main metabolite in tissues) by glutamine synthesis in the skeletal muscles, liver, brain, myocardium, and other organs. Other metabolites of ammonia N 13 include small amounts of N 13 amino acid anions (acidic amino acids) in the forms of glutamate N 13 or aspartate N 13.
Ammonia N 13 is eliminated from the body by urinary excretion mainly as urea N 13.
The pharmacokinetics of Ammonia N 13 Injection have not been studied in renally impaired, hepatically impaired, or pediatric patients.
In a descriptive, prospective, blinded image interpretation study2 of adult patients with known or suspected coronary artery disease, myocardial perfusion deficits in stress and rest PET images obtained with Ammonia N 13 (N=111) or Rubidium 82 (N=82) were compared to changes in stenosis flow reserve (SFR) as determined by coronary angiography. The principal outcome of the study was the evaluation of PET defect severity relative to SFR.
PET perfusion defects at rest and stress for seven cardiac regions (anterior, apical, anteroseptal, posteroseptal, anterolateral, posterolateral, and inferior walls) were graded on a 0 to 5 scale defined as normal (0), possible (1), probable (2), mild (3), moderate (4), and severe (5) defects. Coronary angiograms were used to measure absolute and relative stenosis dimensions and to calculate stenosis flow reserve defined as the maximum value of flow at maximum coronary vasodilatation relative to rest flow under standardized hemodynamic conditions. SFR scores ranged from 0 (total occlusion) to 5 (normal).
With increasing impairment of flow reserve, the subjective PET defect severity increased. A PET defect score of 2 or higher was positively correlated with flow reserve impairment (SFR<3).
Ammonia N 13 Injection is packaged in 30 mL multiple dose glass vial containing between 1.11 GBq to 11.1 GBq (30 mCi to 300 mCi) of [13N] ammonia, at the end of synthesis (EOS) reference time, in 0.9% sodium chloride injection solution in approximately 8 mL volume. The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of 0.5-1.0 picomoles (8.47-16.94 picograms) of Ammonia.
Instruct patients to drink plenty of water or other fluids (as tolerated) in the 4 hours before their PET study.
Instruct patients to void after completion of each image acquisition session and as often as possible for one hour after the PET scan ends.
Manufactured and Distributed by:
University of Texas Southwestern Medical Center
5323 Harry Hines Blvd.
Dallas, TX 75390-7201
Revised: February 2017
Ammonia N 13 Injection, USP
3.75 mCi/mL to 37.5 mCi/mL @ EOS*
Activity @ EOS*: Total __________mCi Volume __________mL
Calibration (EOS*) Time
Diagnostic - For Intravenous Use Only
(Expires 50 minutes after EOS*)
0.138 GBq to 1.387 GBq (3.75 mCi/mL to 37.5
mCi/mL)of no-carrier added Ammonia N 13 @ EOS*in
0.9% Sodium Chloride Injection.
Store at 25ºC (77ºF); (see insert)
Store upright in a shielded container.
Aseptically withdraw and handle doses.
[13N] Half-Life = 9.96 minute
Calculate correct dosage from date and
time of calibration.
Do not use if cloudy or if it contains particulate matter.
*EOS = End of Synthesis
CAUTION: RADIOACTIVE MATERIAL
Manufactured: University of Texas
Southwestern Medical Center
5323 Harry Hines Blvd
Dallas, TX 75390-7201
ammonia n-13 injection, solution
|Labeler - The University of Texas Southwestern Medical Center (800771545)|
|The University of Texas Southwestern Medical Center||800771545||positron emission tomography drug production(70681-001) , ANALYSIS(70681-001) , LABEL(70681-001)|